Tissue-Targeted Drug Delivery Strategies to Promote Antigen-Specific Immune Tolerance

During autoimmunity or organ transplant rejection, the immune system attacks host or transplanted tissue, causing debilitating inflammation for millions of patients. There is no cure for most of these diseases. Further, available therapies modulate inflammation through nonspecific pathways, reducing symptoms but also compromising patients' ability to mount healthy immune responses. Recent preclinical advances to regulate immune dysfunction with vaccine-like antigen specificity reveal exciting opportunities to address the root cause of autoimmune diseases and transplant rejection. Several of these therapies are currently undergoing clinical trials, underscoring the promise of antigen-specific tolerance. Achieving antigen-specific tolerance requires precision and often combinatorial delivery of antigen, cytokines, small molecule drugs, and other immunomodulators. This can be facilitated by biomaterial technologies, which can be engineered to orient and display immunological cues, protect against degradation, and selectively deliver signals to specific tissues or cell populations. In this review, some key immune cell populations involved in autoimmunity and healthy immune tolerance are described. Opportunities for drug delivery to immunological organs are discussed, where specialized tissue-resident immune cells can be programmed to respond in unique ways toward antigen. Finally, cell- and biomaterial-based therapies to induce antigen-specific immune tolerance that are currently undergoing clinical trials are highlighted.

Automated summary

During autoimmunity or organ transplant rejection, the immune system attacks host or transplanted tissue, causing inflammation. Recent advances in vaccine-based antigen-specific therapies offer promising opportunities for treating autoimmune diseases and transplant rejection. Precision and combinatorial delivery of antigens, cytokines, small molecule drugs, and immunomodulators can be facilitated by biomaterial technologies.